Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Treatment of Down syndrome in mice restores nerve growth in cerebellum

25.01.2006


Researchers at Johns Hopkins restored the normal growth of specific nerve cells in the cerebellum of mouse models of Down syndrome (DS) that were stunted by this genetic condition. The cerebellum is the rear, lower part of the brain that controls signals from the muscles to coordinate balance and motor learning.



The finding is important, investigators say, because the cells rescued by this treatment represent potential targets for future therapy in human babies with DS. And it suggests that similar success for other DS-related disruptions of brain growth, such as occurs in the hippocampus, could lead to additional treatments - perhaps prenatally - that restore memory and the ability to orient oneself in space.

DS is caused by an extra chromosome 21, a condition called trisomy - a third copy of a chromosome in addition to the normal two copies. Children with DS have a variety of abnormalities, such as slowed growth, abnormal facial features and mental retardation. The brain is always small and has a greatly reduced number of neurons.


A report on the Hopkins work with trisomic mice, led by Roger H. Reeves, Ph.D., professor in the Department of Physiology and the McKusick-Nathans Institute for Genetic Medicine at Hopkins, appears in the January 24 issue of the Proceedings of the National Academy of Sciences (PNAS).

Reeves and his team used an animal model of DS called the Ts65Dn trisomic mouse to show that pre-nerve cells called granule cell precursors (GCP) fail to grow correctly in response to stimulation by a natural growth-triggering protein. This protein, called Sonic hedgehog (Shh), normally activates the so-called Hedgehog pathway of signals in these cells. These signals stimulate mitosis (cell division) and multiplication of the cells in the growing, newborn brain, according to the researchers.

The GCP originate near the surface of the cerebellum and migrate deeper into the brain to form the internal granule layer (IGL), the researchers note. Therefore, the team studied the growth of the cerebellum in Ts65Dn trisomic mice at seven time points -- beginning at birth - to determine when GCP abnormalities first occurred. The IGL was similar in both normal and Ts65Dn mice at birth, but was significantly reduced in the trisomic mice by day six after birth.

Furthermore, the researchers found that the reduced number of GCP in these mice compared to normal mice was not due to cell death; rather, there were 21 percent fewer GCP undergoing cell division in Ts65Dn mice. This suggested that stimulating these cells might restore normal numbers of GCP, according to Reeves.

The Hopkins team then showed in test-tube experiments that GCP from the brains of Ts65Dn mice had a significantly lower response to increasing concentrations of a potent form of Shh called ShhNp. That is, increasing concentrations of ShhNp triggered increasing rates of mitosis. Despite their lower response, trisomic cells did show a dose response with increasing ShhNp concentrations.

"The fact that trisomic GCP responded to stimulation of their Hedgehog pathway even in a reduced way is significant," says Reeves, the senior author of the PNAS paper. "It suggested that these cells could be stimulated to reach normal levels of cell division by artificially increasing their exposure to Hedgehog growth factor."

Based on this initial discovery, the team injected into newborn Ts65Dn mice a molecule that stimulates the Hedgehog pathway to trigger cell growth. Treatment of the trisomic mice with this molecule, called SAG 1.1, restored both the numbers of GCP and the number of GCP cells undergoing mitosis to levels seen in normal mice by six days after birth.

"The normal mouse cerebellum attains about a third of its adult size in the first week after birth," says Randall J. Roper, Ph.D. "This is the time during which SAG 1.1 treatment of Ts65Dn restored GCP populations and the rate of mitosis of those cells," he adds. "However, further research is needed to determine if it’s possible to reverse the effects of trisomy in other parts of the DS mouse." Roper is a postdoctoral fellow in the laboratory of Reeves and a co-first author of the PNAS paper.

Gary Stephenson | EurekAlert!
Further information:
http://www.jhmi.edu
http://www.hopkinsmedicine.org/mediaII/RSSinstructions.html

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>